Fueling or Fighting Cancer? The Thermogenic Paradox of Brown Adipose Tissue

Figures

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  Fig. 1. Adipocyte phenotypes and metabolic consequences of BAT activation and browning. The diagram contrasts white, beige, and brown adipocytes and summarizes how environmental cues shape their function. White adipocytes store triglycerides, are UCP1-negative, contain one large lipid droplet, and have low mitochondrial density. Cold exposure and beta-adrenergic stimulation promote browning toward a beige phenotype, which increases mitochondrial content and thermogenic capacity. Brown and beige adipocytes are UCP1-positive, contain multiple small lipid droplets, and dissipate energy as heat. Innervation and vascularization support this thermogenic program, which tends to decline with age. Thermoneutral conditions and a high-fat diet favor whitening. Adipocyte states are linked to systemic outcomes, including energy expenditure, insulin sensitivity, appetite regulation, leptin and adiponectin secretion, cell proliferation, inflammation, and risk of metabolic disease. The figure was created with BioRender.com; a publication license was obtained

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  Fig. 2. Regulatory pathways potentially involved in the promotion of browning and BAT activation in the context of cancer. Environmental and nutritional cues, such as cold exposure, exercise, nutrient deprivation, nitric oxide, and dietary signals, engage upstream sensors and receptors, including beta-adrenergic receptors, VEGF signaling, AMPK, and TRPV1. These inputs converge on canonical pathways, notably beta-adrenergic, nitric oxide, and WNT signaling, and activate the transcriptional coactivator PGC-1α through mediators such as CREB, CaMK, and SIRT1. PGC-1α partners with transcription factors including PPARGC1A, ESRRA, NRF1, NRF2, MEF2A, and PPARG to induce genes that drive mitochondrial biogenesis, thermogenesis, and lipid handling. The resulting program increases energy expenditure and supports the browning of white adipocytes. Mitochondrial remodeling is central to this process, with UCP1 serving as a key effector of thermogenesis and lipid flux. In carcinogenesis, tumor- and host-derived cues can modulate these networks, thereby influencing adipose remodeling and systemic metabolism. The figure was created with BioRender.com; a publication license was obtained